Cyclic octapeptide neuromedin B receptor antagonists

US5569741A · kind A · utility

Assignees

• Biomeasure, Incorporated · US
• The Administrators of the Tulane Educational Fund · US

Inventors

• David H. Coy · New Orleans, US
• John E. Taylor · Upton, US

Key dates

• Filing date: Dec 8, 1994
• Grant date: Oct 29, 1996
• Expiry date: Dec 8, 2014

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K14/6555
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A cyclic octapeptide of the formula: ##STR1## wherein: A.sup.1 is D-Nal or D-Trp; A.sup.3 is Phe, F.sub.5 -Phe, or X-Phe wherein X is a halogen, NO.sub.2, CH.sub.3, or OH; A.sup.5 is --NH--CH(Y)--CO-- wherein Y is (CH.sub.2).sub.m --R.sub.4 --N(R.sub.5)(R.sub.6) or (CH.sub.2).sub.n --R.sub.4 --NH--C(R.sub.7)--N(R.sub.5) (R.sub.6); A.sup.6 is the D-- or L-- isomer of Thr, Leu, Ile, Nle, Val, and Abu; A.sup.8 is Nal or Trp; m is 1, 2, or 3; n is 1, 2, 3, 4 or 5; each of R.sub.1 and R.sub.2, independently, is H, E, COE, or COOE wherein E is C.sub.1-12 alkyl, C.sub.2-12 alkenyl, C.sub.2-12 alkynyl, phenyl, naphthyl, C.sub.7-12 phenylalkyl or alkylphenyl, C.sub.8-12 phenylalkenyl or alkenylphenyl, C.sub.8-12 phenylalkynyl or alkynylphenyl, C.sub.11-20 naphthylalkyl or alkylnaphthyl, C.sub.12-20 naphthylalkenyl or alkenylnaphthyl, or C.sub.12-20 naphthylalkynyl or alkynylnaphthyl, provided that when one of R.sub.1 or R.sub.2 is COE or COOE, the other must be H; R.sub.4 is C.sub.6 H.sub.4 or absent; R.sub.7 is .dbd.NR.sub.8, .dbd.S, or .dbd.O; and each of R.sub.3, R.sub.5, R.sub.6, and R.sub.8, independently, is H or E.